65P - GIRK1 overexpression correlates with ER positive breast cancer subtypes and is associated with poor prognosis

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Sarah Kammerer
Citation Annals of Oncology (2015) 26 (suppl_3): 15-24. 10.1093/annonc/mdv117
Authors S. Kammerer1, A. Sokolowski1, H. Hackl2, D. Platzer1, S. Jahn3, F. Peintinger3, F. Symmans4, W. Schreibmayer1, T. Bauernhofer5
  • 1Institute Of Biophysics, Medical University Graz, 8010 - Graz/AT
  • 2Division Of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck/AT
  • 3Institute Of Pathology, Medical University Graz, Graz/AT
  • 4Department Of Pathology, MD Anderson Cancer Center, Houston/US
  • 5Division Of Oncology, Medical University Graz, Graz/AT

Abstract

Body

Background/aim: In order to improve patient care it is important to investigate the potential use of novel prognostic biomarkers for breast cancer. Overexpression of GIRK1 (G protein-activated inward rectifier potassium channel 1) mRNA and protein in tumours of breast cancer patients has been correlated with lymph node metastases and poor prognosis in previous studies with small patient numbers. The aim of this study was to validate the use of GIRK1 as prognostic breast cancer biomarker.

Methods: To study GIRK1 expression, gene expression data of breast carcinoma available from the cancer genome atlas (TCGA, n = 905) and of a data set of estrogen receptor (ER) positive breast cancer patients including also patients of the Medical University of Graz (GEO-ID: GSE17705, n = 298) were analysed using SigmaStat/SigmaPlot, R and Genesis.

Results: Analysing the TCGA set, we found that GIRK1 mRNA expression levels were significantly higher in breast tumours compared to corresponding normal tissue (n = 105, p < 0.001). Furthermore, GIRK1 was significantly overexpressed in tumours of ER positive patients compared to ER negative patients (n = 841, p < 0.001). Spearman rank correlation and hierarchical cluster analysis strongly supported the link between GIRK1 overexpression and ER positive breast cancer subtypes in both data sets studied. ER positive patients with high GIRK1 mRNA levels had a worse overall survival probability than ER positive patients with lower GIRK1 levels (n = 609, p < 0.05, HR = 1.71) in the TCGA set. Clinical follow-up data collection of the second data set is still ongoing, but interim analysis showed a trend towards worse overall survival probability for patients with high GIRK1 mRNA levels (n = 99, p = 0.064, HR = 1.7).

Conclusion: The analysis of two large gene expression sets indicates that GIRK1 mRNA overexpression strongly correlates with ER positive breast cancer subtypes and worse prognosis in ER positive patients. Therefore, GIRK1 might become a new prognostic biomarker for ER positive breast cancer. In order to provide a diagnostic tool to examine GIRK1 expression levels of breast cancer patients in daily practice, we are planning to establish an RNA in situ hybridization protocol for GIRK1.

Disclosure: All authors have declared no conflicts of interest.